Pathways of nucleic acid metabolism and innate immune sensing (WP4705)
Cytosolic DNA and RNA can lead to innate immune sensing via three paths. DNA is sensed by cGAS, which activates STING. RNA is sensed by MDA5 and RIG-I, which activates MAVS. An activation of STING or MAVS lead to phosphorylation of IFR3, which triggers innate immune responses. This pathway was inspired by Chapter 14 of the 5th edition of the book of Blau (in press).
AuthorsDenise Slenter , Laurent Winckers , Egon Willighagen , and Eric Weitz
Discuss this pathway
- Bioinformatics and systems-biology analysis to determine the effects of Coronavirus disease 2019 on patients with allergic asthma (2022).
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OrganismsHomo sapiens Inherited Metabolic Disorders (IMD) Pathways
Pathway Ontologysignaling pathway in the innate immune response altered DNA repair pathway
|cGAS which signals via STING (encoded by TMEM173)
|RNase H2subunit A
|Cytosolic deoxyribonuclease anchored in the outer nuclear membrane. A lack of TREX1 causes DNA accumulation, both within the nucleus and the cytosol.
|Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing
|mitochondrial antiviral signaling (MAVS)
|Cytosolic RNA sensorActivating mutations in RIG-I and MDA5 increase receptor affinity resulting in constitutive type I IFN signaling.
|cytosolic RNA sensorActivating mutations in RIG-I and MDA5 increase receptor affinity resulting in constitutive type I IFN signaling.
|RNase H2subunit B
|RNase H2subunit C
|SAMHD1 has also ribonuclease activity, suggesting that a loss of SAMHD1 may lead to RNA accumulation.
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- Mammalian retroelements. Deininger PL, Batzer MA. Genome Res. 2002 Oct;12(10):1455–65. PubMed Europe PMC Scholia
- Requirement of dimerization for RNA editing activity of adenosine deaminases acting on RNA. Cho DSC, Yang W, Lee JT, Shiekhattar R, Murray JM, Nishikura K. J Biol Chem. 2003 May 9;278(19):17093–102. PubMed Europe PMC Scholia